TELOMERASE REGULATION DURING ENTRY INTO THE CELL-CYCLE IN NORMAL HUMAN T-CELLS

Telomerase activity is involved in telomere length maintenance. Leukoc ytes, unlike many human somatic tissues, have detectable telomerase ac tivity. These cells provide a normal human cell type in which to study telomerase. We studied the regulation of telomerase activity and the telomerase RNA component as leukocytes were stimulated to enter the ce ll cycle. In primary human leukocytes stimulated with phytohemagglutin in, telomerase activity increased >10-fold as naturally quiescent cell s entered the cell cycle. Antibodies to the T cell receptor (TCR)/CD3 complex and the costimulatory CD28 receptor induced telomerase activit y in a T cell-enriched population of cells. Rapamycin, an immunosuppre ssant that blocks TCR/CD3 signal transduction pathways and cdk2 activa tion, blocked telomerase induction. Hydroxyurea, an inhibitor of S pha se, did not block cdk2 kinase activity or telomerase activation. In su mmary, telomerase is regulated in G1 phase as normal human T cells ent er the cell cycle.